Despite great advances in the prevention and control of cardiovascular diseases (CVD), largely attributable to the widespread use of statins, cardiovascular (CV) risk remains exceptionally high, particularly among the elderly (>65 years) and those with comorbid conditions such as diabetes. Efforts to enhance the therapeutic benefits of statins with combination therapy that includes niacin or fenofibrate have not succeeded. It is thus critical to identify strategies that improve the therapeutic benefits of statins. Alcohol intake, while not recommended as an intervention for disease prevention, serves as an excellent model to study a common dietary factor with high likelihood to impact response to statin therapy in terms of CV benefits. Our preliminary studies show that moderate alcohol use significantly improves statin efficacy with regard to all-cause mortality. Heavy drinking could lower efficacy of statins through biological interactions or poor adherence to statins. The net effect of alcohol use at moderate and heavy levels on the risk of CV events or mortality is not known, despite the growing number of people who are aging and are exposed to both alcohol and statins. In this secondary data analysis we seek to investigate whether alcohol alters the outcomes of statin therapy in the general population so as to determine whether it may be necessary to counsel patients about alcohol when statins are prescribed. If we confirm a strong influence of moderate alcohol intake on enhancing statin efficacy, we will move the field of CVD prevention forward, not by endorsing or encouraging alcohol consumption, but by providing leads for research into specific mechanisms to be translated into pharmaceutical compounds that mimic this specific alcohol effect. Such compounds could be used as adjuncts to statin therapy. Furthermore, if the study confirms the preliminary evidence of reduced statin efficacy with heavy alcohol use, it will provide the basis for updating guidelines on statin use by encouraging health practitioners to aggressively counsel patients to quit alcohol or shift from heavy to moderate alcohol intake. According to CDC (MMWR Jan 7, 2014), only one in six US adults report ever discussing alcohol use with a healthcare provider, an observation that could in part be explained by limited data on effects of alcohol on health, especially in individuals without liver disease. Currently there are no large published studies that have investigated the effect of alcohol on statin efficacy with regard to clinical CVD events. Our specific aims are: (1) to determine whether alcohol consumption modifies the efficacy of statin therapy as measured by mortality and incident CVD events, (2) to determine whether the effect of alcohol consumption on the CV benefits of statins varies by age and gender, variables known to significantly modify alcohol metabolism, and (3) to determine, through mediation analysis, the potential mechanisms or pathways through which alcohol may modify effects of statins. This study, among >120,000 men and women, will bring solid evidence on whether modulation of alcohol intake is relevant to statin therapy, identify modifying effects on specific CVD events, and enable prioritization of areas for mechanistic studies.